The development of auditory brain stem neurons and their connections is the main theme under investigation in this laboratory. The major emphasis of the proposed research is the study of auditory nerve (primary afferent) influences on the migration and differentiation of precochlear neurons (neurons destine to be incorporated into the cochlear nuclei). Two specific studies are presented. 1). The investigation of a mammalian model that will allow access to the early stages of neural differentiation in the auditory brain stem for the purpose of experimental manipulation. In this study, the identity of the precochlear neurons, described in the North American opossum, will be verified in the more readily available, rat-sized opossum, Monodelphis domestica. Axonal transport of horseradish peroxidase from the posterior tectum will be utilized to label neurons in the precochlear band as they migrate laterally across the medulla to enter the cochlear nuclei. A timetable of this migration will be established. Based on these data, a second experiment will be designed. 2.) Interruption or the auditory nerve fibers prior to their reaching the precochlear neurons and the study of the subsequent differentiation of the precochlear neurons devoid of their auditory nerve contacts. Auditory nerve fibers will be labeled with HRP in an age-graded series of animals and the time recorded at which they first become juxtaposed with the precochlear neurons. In a second age-graded series of pups, the spiral ganglion will be cauterized to interrupt the auditory nerve fibers. After an appropriate period of growth, the soma size and position as well as primary dendrite orientation of the differentiating precochlear neurons will be recorded. From these data it will be possible to define the affects of the afferent removal. Knowledge of primary afferent fiber influences on neuron growth and differentiation will be of significance in accessing congenital defects in the auditory system and in the design of appropriate replacement therapy.